HEMATOPOIETIC AND IMMUNE CANCER BIOLOGY (HICB) REASEARCH PROGRAM PROJECT SUMMARY/ABSTRACT The objectives of the Hematopoietic and Immune Cancer Biology (HICB) Program are to improve cancer diagnosis, care and cure rates through better understanding of molecular pathogenesis of blood neoplasms and optimizing the efficacy of cellular immunotherapy and stem cell transplantation (SCT). Program members investigate the roles of hematopoietic processes in health and disease, including the evolution of hematologic neoplasms from normal hematopoiesis and the roles of cellular immunity in cancer immune responses, especially toward developing new treatments for hematological malignancies. The program is organized around 3 scientific aims: (1) Discover novel molecular features of hematologic neoplasms to improve diagnosis, prognostication, and develop a new generation of rationally-targeted therapeutic approaches, (2) Interrogate mechanisms of tumor immune surveillance and evasion to develop and apply new anti-tumor cell- based immune therapies, and (3) Develop and administer an innovative portfolio of clinical trials based on rationally-targeted molecular, cellular and immune cancer therapeutics. These aims reflect major working groups and initiatives that coalesces program members with other Cancer Center investigators through inter- programmatic collaborations that result in preclinical and clinical research efforts, grants, and trial protocols. Extensive use of an array of shared resources, in particular, Genomics, Hematopoietic, Cytometry, Athymic, Biostatistics, Transgenic, Tissue, and Translational Research facilitate all aspects of member discoveries. Under the leadership of Jaroslaw Maciejewski (Co-Leader), Marcos de Lima (Co-Leader) and Alex Huang (Co-Leader) the HICB Program has 59 members including 32 full, 7 associate, and 20 clinical members representing 18 different departments across all 3 consortium institutions. Members are funded with a total of $13.4M in grant funding (annual direct costs), of which $8.9M is peer-reviewed and $2.2M is NCI-funded. Between 2012 and 2016, HICB program members published 1,264 publications. Cancer and program related publications included 17% inter-programmatic, 24% intra-programmatic, 5% inter- and intra-programmatic and 6% that involved collaborations with another Cancer Center. This highly effective program has made major practice-changing contributions benefiting cancer patients. Examples include: the discovery of novel driver genes in the evolution of MDS leading to improved disease classification and molecular prognostication; new and effective strategies for MDS treatment emerged using demethylating agents; and members have led a SWOG study identifying significant survival advantage for Inotuzumab ozogamicin in relapsed/refractory ALL.